Pain Management and Palliative Care in HIV,AIDS Patients

Pain Management and Palliative Care in HIV/AIDS Patients Timothy L. Sternberg, DMD, MD Director, Center for Pain Management University of Florida/Shands Jacksonville Disclosure of Financial Relationships This speaker has no significant financial relationships with commercial entities to disclose. This slide set has been peer-reviewed to ensure that there are no conflicts of interest represented in the presentation. Pain & Palliative Care in HIV/AIDS Objectives 1. Pain incidence and prevalence 2. Barriers to effective pain & symptom management 3. Assessing pain in HIV & AIDS 4. HIV/AIDS specific painful syndromes 5. General pain management guidelines 6. Specific treatment strategies HIV/AIDS Pain Etiologies • • • • • HIV tissue damage Opportunistic Infections Malignancies Side effect of treatment Incidental to HIV disease Is pain in HIV/AIDS patients common? 1. Not a concern to most patients who just want their disease cured. 2. Only common in terminal AIDS. 3. Only common with high viral loads. 4. Common in all stages of the disease. 5. No: Adequately treated with current available care. Prevalence of Pain in HIV/AIDS • 28% asymptomatic HIV seropositive men • 56% AIDS-related complex • 80% AIDS » (Singer, 1993) • 97% terminal » (Singh 1992) • 57-61% hospitalized AIDS patients • 2nd most common admitting problem » (Lebovits 1989, 1994) Prevalence of Pain in HIV/AIDS • Average 2.5 different pains • Severity: 5.4 (average) – 7.4 (worse) / 10 NRS • Prevalence correlated: – – – – CDC category Number of current HIV related symptoms Treatment for HIV related infections Absence of antiretroviral therapy • Intensity correlated: – Females – Non-Caucasions (Breitbart 1996) Prevalence of Pain in HIV/AIDS • Pre-HAART 56-80% • Prevalence Post-HAART – Estimate of 30% (Newshan, Bennett, Holman, 2000) Prevalence of Pain in HIV/AIDS • Prevalence and Intensity associated with: – Greater impairment functional ability – Physical symptom distress – Psychological morbidity Barriers to Pain Management • Pain generally under-treated in HIV/AIDS pts • Particularly patients with IV drug abuse hx • Only 15% ambulatory AIDS pts received adequate analgesia • Only 6% with severe pain Rx’d opioids • Under-treatment 85% (cancer 42%) • Women & minorities more likely under-treated (Brietbart 1994) Barriers to Pain Management • • • • Patient related barriers Clinician related barriers System related barriers HIV specific barriers What is the most common barrier to adequate pain management in HIV/AIDS? 1. 2. 3. 4. 5. Fear of addiction Poor compliance Governmental restrictions Poor patient assessment Inadequate application of knowledge and therapeutic modalities currently available Barriers to Pain Management • Patient related barriers – Fear of addiction – Misconceptions about tolerance – Concern about side effects – Fear of correlation with disease progression – Poor compliance with antiviral medications Barriers to Pain Management • Clinician related barriers – Misconceptions of addiction, dependence, and tolerance – Inadequate training – Inadequate patient assessment – Poor pharmacologic knowledge – Inadequate application of knowledge and therapeutic modalities currently available Barriers to Pain Management • System related barriers – Regulatory issues – Pharmacy restrictions – Governmental restrictions – Economic issues HIV/AIDS Specific Barriers • Many African Americans consider Hospice second class care • Unfamiliarity with medical system • Inner city prevalence of illicit drug use • Continued illicit drug use • Poverty – Poor access to phones, refrigerators, housing • Poor compliance with antiviral therapy Assessing Pain in HIV & AIDS • Pain history – – – – Intensity Location Qualities Radiation • • • • • Work-up possible etiologies Rule out infections and malignancies Consider multiple concurrent etiologies Thorough H&P Eval psychological/emotional/social factors Characterizing Pain in HIV/AIDS • Nociceptive – Somatic • w, w/o inflammation – Visceral • Neuropathic – Central – Peripheral – Sympathetic Assessing Pain in HIV & AIDS Etiologies • HIV related – tissue damage – infection – tumors • HIV treatment – Medications – Chemotherapy, radiation • Unrelated to HIV Which locations are relatively unaffected by HIV related pain? 1. 2. 3. 4. 5. Head and face Chest Abdomen Pelvis Musculoskeletal system Common Painful HIV/AIDS Syndromes • • • • • • • • • • • Headaches Oral cavity Throat pain Chest pain Abdominal pain Anorectal pain Peripheral neuropathy Musculoskeletal system Herpes zoster/PHN Social pain Psychological pain 46% 53% 20% 41% 12-26% 34% 25% (10-50%) 72% 5% HIV/AIDS Headache Syndromes • HIV specific – – – – – – – – – – Aseptic meningitis with acute infection CNS lymphoma Metastatic Kaposi’s sarcoma Infections: HSV, CMV, Toxoplasmosis, TB, Syphilis HIV encephalitis Zidovudine Efavirenz Emtricitabine Stavudine Tenofovir • HIV treatment • Concurrent illness – Tension-type, Migraines – Sinus infections HIV/AIDS Oral-pharyngeal Syndromes – Candidiasis 28%-75% – Necrotizing gingivitis – HSV, CMV, HIV, EBV ulcers – Recurrent aphthous ulcers – Zalcitabine ulcers – Kaposi’s sarcoma – Dental abscesses Oral-pharyngeal Candidiasis HIV/AIDS Oral-pharyngeal Syndromes • Interferes with oral hygiene – More oral pharyngeal pathology • Interferes with nutritional intake – Wasting syndrome AIDS/HIV Related Oral Pathology HIV/AIDS Chest Pain Syndromes • Incidence 41% • Pneumocystis carinii pneumonia – Retrosternal, burning • Esophagitis (+/- dysmotility) – Candidiasis – HSV, CMV, HIV ulcerations – GERD • Herpes Zoster- Post Herpetic Neuralgia Herpes Zoster- Post Herpetic Neuralgia HIV/AIDS Abdominal Pain Syndromes • Nausea – NRTI’s: zidovudine, didanosine, emtricitabine, lamivudine, tenofovir • Diarrhea – Infectious – NRTI’s: tenofovir, emtricitabine, • • • • • • • CMV ileitis, colitis Visceromegaly (didanosine) Pancreatitis (pentamidine, ddI, ddC, ) Acalculous cholecystitis Schlerosing cholangitis (“AIDS cholangitis”) CMV bowel perforation Tumor: Kaposi’s, Lymphoma HIV/AIDS Anorectal Pain Syndromes – Affect 34% AIDS/ARC males – Infections/STD’s – Trauma – Fistulae/fissures/abscesses – Rectal cancers • KS, NHL, SSC HIV/AIDS Anorectal Pain Syndromes HIV/AIDS Gynecologic Pain Syndromes – STD’s – Herpes simplex ulceration – Human papilloma virus – Cervical cancer – Pelvic inflammatory disease HIV/AIDS Gynecologic Pain Syndromes HIV/AIDS Pain Syndromes Peripheral Neuropathies • • • • Acute inflammatory demyelinating polyneuropathy Chronic inflammatory demyelinating polyneuropathy Mononeuritis multiplex Radiculitis – VZV: Herpes Zoster & post-herpetic neuralgia – CMV – HIV – HIV (AIDS associated distal sensory neuropathy) – Toxic (Antiretroviral toxic neuropathy) – Vitamin deficiencies • Distal symmetrical peripheral neuropathy Distal Symmetrical Peripheral Neuropathy • Most common HIV/AIDS neuropathy • Usually late complication • Sensory: predominantly small fiber – Pain, paresthesias soles of feet • Signs: large fiber • Etiology: HIV infection or treatment • Risk Factors: - AIDS Associated Distal Sensory Neuropathy - Antiretroviral toxic neuropathy (NRTI’s) – Reduced Achilles DTR/vibration sense • age, high viral load, low CD4 count, cumulative NRTI dose Common Painful HIV/AIDS Syndromes Musculoskeletal system • Arthropathies – Reactive arthritis • Reiter’s syndrome – Non-specific arthralgias – Psoriatic arthritis – HIV arthritis – Septic arthritis Common Painful HIV/AIDS Syndromes Musculoskeletal system • Myopathies – Inflammatory polymyositis • Subacute proximal weakness and myalgia • HIV and other virus, infection vs. inflammation • Zidovudine – Necrotizing non-inflammatory myopathy • Zidovudine – Infectious Myositis • Toxoplasmosis • Microsporidiosis mysositis HIV/AIDS Social Pain • Young • Family estrangement • Social stigma – STD's – Drug use – HIV – Homosexual • Poor coping mechanisms • Limited support “Unos Cuantos Piquetitos”(A Few More Sticks) Frida Kahlo Pain & Palliative Care in HIV/AIDS Management Options • Cognitive-behavioral interventions • Systemic pharmacotherapy -General pain management medications -HIV/AIDS specific pain medications • Interventional techniques • Surgical techniques • Physical Modalities • Electro-stimulation therapy General Pain Management Principles • Thorough assessment – Somatic nociceptive vs. neuropathic pain – Intensity, quality, timing – Exacerbating and relieving factors – Treatment history – Pharmacologic history – Psychosocial modifiers Systemic Pharmacotherapy General Management Principles • • • • By the patient By the syndrome By the clock By the analgesic ladder • Consider drug interactions General Pharmacotherapeutic Principles WHO Analgesic Ladder in HIV/AIDS Nociceptive Neuropathic Analgesic Ladder Optimal Use of Analgesics World Health Organization Step Ladder 1) Begin with non-opiate, nonsteroidal antiinflammatory agents (NSAIDS) 2) Add a “weak” opiate, such as codeine or hydrocodone (with or without an adjuvant) 3) Move to a stronger opiate, such as oxycodone, morphine (with or without an adjuvant) 4) Complementary, non-pharmacologic strategies 5) Interventional strategies WHO Analgesic Ladder in HIV/AIDS • Non-opioid analgesic – Acetaminophen – Tramadol – NSAID • Weak opioids – Propoxyphene – Hydrocodone • Strong opioids – – – – Oxycodone Morphine Hydromorphone (Dilaudid) Fentanyl (Duragesic) Non-Opioid Analgesics Acetaminophen (APAP, Tylenol) Acetylsalicylic acid (Aspirin, ASA) Celecoxib (Celebrex) Choline magnesium trisalicylate (Trilisate) Ibuprofen (Motrin) Indomethacin (Indocin) Naproxen (Naprosyn) Piroxicam (Feldene) Salsalate (Salsitab) Sulindac (Clinoril) Tramadol (Ultram, Ultracette) 325-650mg po q4-6h prn Max: 4000mg/day 325-650mg po q4h prn* Max: 4000mg/day 100-200mg po q12h-qd Max: 400mg/day 500-1500mg po q8-12h prn* Max: 3000mg/day 400-800mg po q4-6h* Max: 3200mg/day 25-50mg po q6-12h prn* Max: 200mg/day 250-500mg po q8-12h prn* Max: 1500mg/day 10-20mg po qd prn* Max: 20mg/day 500-1000mg po q4-8h prn* Max: 4000mg/day 150-200mg po q12h prn* OR 300-400mg po qd prn* Max: 400mg/day 50-100 mg q 6h prn pain Max: 400 mg/day 10-15mg/kg po q4-6h prn Max: 2600mg/day 10-15mg/kg po q4-6h prn Max: 80mg/kg/day $ $ NA 25mg/kg po q12h prn 4-10mg/kg po q6-8h prn Max: 40mg/kg/day OR 2400mg/day 1-2mg/kg po q6-12h prn Max: 4mg/kg/day OR 200mg/day 5mg/kg po q12h prn Max: 1000mg/day 0.2-0.3mg/kg po qd prn Max: 15mg/day NA NA NA $$ $ $$ $ $$ $ $$ $$ NSAID’s Side Effects • Gastric irritation/ulceration • Prolong bleeding time, esp. ASA • CNS stimulation • Hepatic dysfunction • Renal dysfunction • Elevated BP • Edema • Allergic Rxn's Opioid Analgesics Agent Starting Dose for Adults  Starting Dose for Pediatrics  Cost Propoxyphene/APAP (Darvocet-N/100/325) Codeine Codeine/APAP (Tylenol#3) PO : 1-2 q4h prn PO: 30-60mg q4-6h prn IV: 15-30mg q4-6h prn PO: 30-60mg codeine q4-6h prn Max: (based on APAP) 12 tablets or 4000mg/day of APAP from all sources PO: 1-2 tabs po q4-6h prn Max: (based on APAP) 8 tablets or 4000mg/day of APAP from all sources PO: 1mg/kg q4-6h prn IM/SC: 0.5mg/kg q4-6h prn PO: 0.5-1mg/kg codeine q4-6h prn Max: (based on APAP) 10-15mg/kg/dose AND 2600mg/day of APAP from all sources PO: 0.15-0.2mg/kg hydrocodone q6-8h prn Max: (based on APAP) 10-15mg/kg/dose AND 2600mg/day of APAP from all sources PO: 0.15-0.2mg/kg hydrocodone q6-8h prn Max: (based on APAP) 10-15mg/kg/dose AND 2600mg/day of APAP from all sources PO: 0.05-0.15mg/kg q4-6h prn PO: 0.2-0.5mg/kg q4-6h prn IV: 0.05-0.2 mg/kg q2-4h prn NA PO: 0.1-0.2mg/kg q4-12h prn IV: 0.1mg/kg q4-12h prn NA NA IV: 1-4mcg/kg/dose q1-2h prn $ $$ $ Hydrocodone/APAP (Lortab 5/500, (Lortab 7.5/500) (Vicodin 5/325) Oxycodone/APAP (Perocet 5/325 ) $ PO: 1-2 tabs po q4-6h prn Max: (based on APAP) 8 tablets or 4000mg/day of APAPA from all sources PO: 5-10mg q4-6h prn PO: 15-30mg q4-6h prn IV: 4-10mg q 2-6h prn PO: 2-4mg q4-6h prn IV: 1-4mg q4-6h prn PO: 5-20mg q6-8h prn IV: 2.5-10mg q6-8h prn PO: 15-30mg q12h around the clock PO: 20-40mg q12h around the clock 25-200 mcg/h patch, apply to upper torso q72h $ Oxycodone (OxyIR) Morphine immediate release (MSIR) Hydromorphone (Dilaudid) Methadone (Dolophine) Morphine sustained release (MS Contin) Oxycodone CR (OxyContin) Fentanyl (Duragesic) $$ $$ $$ $$ $$ $$$ $$$$ Opioid Analgesics Agent Morphine Oxycodone Hydrocodone Oxymorphone Hydromorphone Methadone Fentanyl Sufentanil Codeine Meperidine DOSE EQUIVALENTS FOR OPIOID ANALGESICS PO (mg) IV (mg) Fentanyl Patch Dose Conversion 24h Oral Morphine 24h IV Moprhine Fentanyl Patch 30 10 Demand (mg/d) Demand (mg/d) (g/h) q72h 20-30 NA 5-10 NA 7.5 7.5-10 NA NA 200 200300 NA 1 1.5 3.25-5 0.1 0.02 130 75-100 45-134 135-224 225-314 315-404 405-494 495-584 585-674 675-764 8-22 23-37 38-52 53-67 68-82 83-97 98-112 113 25 50 75 100 125 150 175 200 Opioid Side Effects CNS -euphoria -dysphoria -confusion -sedation -miosis Respiratory System: -depresses ventilation GI System: - N/V - Constipation -Biliary muscle spasm CV System: -Orthostatic hypotension -Venodilation -Bradycardia (tachycardia with meperidine) GU System: -urinary retention -urinary urgency Cutaneous System: -vasodilation -flushing -pruritis Analgesic Ladder for Neuropathic Pain Opioid analgesic Topical capsaicin, lidocaine +TCA/SRRI, anticonvulsant, topical agent I certainly Anti-arrhythmic Topical capsaicin, lidocaine +TCA/SRRI, anticonvulsant + analgesic Anti-epileptics + TCA/SNRI +/- analgesic Tricyclic Antidepressant Serotonin/NE Reuptake Inhibitor +/- analgesic Anti-neuropathic Pain Medications First Line Medication Gabapentin Lidocaine patch Tramadol TCAs: amitriptyline Nortriptyline Desipramine SRNI’s: Venlafaxine Doluxetine Trade Name Neurontin Lidoderm Ultram, Ultracette Elavil Pamelor Norpramin Beginning Dose 300 mg qhs-tid 5% patch 1-3 q12h 50-100 mg q6h 25 mg qhs Max Dose 3600 mg/day 3 patches q12h 400 mg/d 150 mg/d Effexor XR Cymbalta 37.5-75 mg qd 60 mg qd 225 mg/d 120 mg/d Anti-neuropathic Pain Medications Second Line Medication Trade Name Beginning Dose Cautions Anticonvulsants Lamotrigine Carbamazepine Oxcarbazepine Topiramate Valproic acid Lamictal Tegretol Trileptal Topamax Depakote SR 50 mg/d 200 mg bid 300 mg bid 200 mg bid 124 mg qd Stevens-Johnson Aplastic anemia Acute glaucoma Hepatotoxicity Capsaicin 0.025-0.075% SSRI’s Mexilitine Clonidine Zostrix Prozac, Paxil Zoloft, Celexa Mexitil Catapress Q4h 20-50 mg qd 150 mg bid 0.1 mg bid Burning pain 2-3 wks Hepatotoxicity Leukopenia Hypotension Antineuropathic Medications Efficacy Oral agents: TCA’s (2.64) > opioids (2.67) > gabapentin (4.29) > tramadol (4.76) > pregabalin (4.93) Topical agents: aspirin/diethyl ether (1.83) > lidocaine patch (2) > capsaicin (3.26) (Numbers needed to treat) e.g., PHN Systemic Pharmacotherapy Antiretroviral-Analgesic Interactions • Fentanyl: Clearance decreased by ritonavir • Methadone: Withdrawal reported with nevirapine, efavirenz • Phenytoin, Carbamazepine: reduced levels/efficacy of NNRTI’s/protease inhibitors • TCA’s/trazadone: inhibited metabolism by ritonavir • Benzodiazepines: Enhanced sedation with ritonavir, protease inhibitors Are treatment with opioids in a patient with a past history of addiction contra-indicated? • Yes • No Opioid Treatment with Chemical Addiction • Diagnose pain syndrome and pathway • Differentiate dependence, tolerance, addiction, and pseudo-addiction • Maximize non-opioid medications • One clinic - one doctor - one pharmacy - one month • Written agreements • Long-acting or controlled release formulations “My Nurse and I” Frida Kahlo Specific Treatment Headache Syndromes • Primary headaches - Abortive: acetaminophen, NSAID's Migraines: triptans (5HTS antagonists) - Prophylactic: TCA's, b-blockers, Ca++ channel blockers • • Zizovudine/NRTI associated HA - Resolves with discontinuance Cerebral toxoplasmosis - sulfadiazine 1-4 gm/d with pyrimethamine (Daraprim) 50-75 mg/d • Cryptococcal meningitis - fluconozole (Diflucan) 12 mg/kg/d, then 6 mg/kg/d • Cerebral lymphoma - steroids/radiation • Nystatin Specific Treatment Oral-pharyngeal Syndromes: Candidiasis – (Mycostatin) 100,000 u/ml, 5 ml qid swish and swallow – Vaginal suppositories, Dissolve in mouth qid • Clotrimazole – (Mycelex) troches 10 mg, Dissolve in mouth 5x/d • Ketoconazole – (Nizoral) 200 mg, 1 qd, Maintenance – Hepatoxicity • Fluconozole – (Diflucan) 100 mg, 2 stat, then 1 qd – Less toxic, expensive • Itraconazole (Sporanox) – Soln 10mg/ml, 10 ml bid swish and swallow – 100 mg tabs bid – Hepatoxicity Specific Treatment Oral-pharyngeal Syndromes • Aphthous ulcer stomatitis – – – – Nonsteroidal aphthasol (Amlexanox) 5% qid Non steroidal Orabase qid Triamcinolone (Kenalog in Orabase) 0.1% qid Dexamethasone (Decadron) elixir 0.5mg/5ml rinse and expectorate qid – Diphenhydramine/AlOH,MgOH (Benadryl/Maalox) 30/60 ml 5 mg swish and swallow tid before meals – Diphenhydramine/sucrulfate (Benadryl/Carafate) 30/60 ml 5 mg swish and swallow tid before meals • Periodontal/periapical abscesses – – – – Dental treatment Pen VK 250-500 mg qid Erythromycin 250 mg qid Cephalexin (Keflex) 250-500 mg qid Specific Treatment Oral-pharyngeal Syndromes • Primary (acute) herpetic (HSV) gingivostomatitis – acyclovir (Zorivax) 200 mg tabs, 2 tid x 7days • Recurrent herpes simplex – penciclovir (Denavir) cream 1% q2h x 4d – docosanol (Abreva) cream (OTC) 5x/d x 4d • Shingles (HVV): acute herpes zoster – acyclovir (Zorivax) 800 mg caps, 1 5x/d x 7days – valacyclovir (Valtrex) caps 500 mg 2 tid x 7 d – Sympathetic plexus (stellate ganglion) blocks Stellate Ganglion Block Specific Treatment Chest Pain Syndromes • Pneumocytis carinii pneumonia - TMP/SMX • Candidiasis - Ketoconazole (Nizoral) 200 mg qd maintenance - Fluconozole (Diflucan) 100 mg, 2 stat, then 1 qd -less toxic, expensive • Herpes simplex esophagitis - Acyclovir (Zorivax) 200 mg tabs, 2 tid x 7days • Herpes zoster/PHN - Acyclovir, TCA's, Gabapentin -Epidural steroid injections -Sympthetic (stellate ganglion) blocks Specific Treatment Esophagitis • Underlying cause • CMV esophagitis- Ganciclovir (Cytovene) 1000 mg tid • Topical lidocaine • Proton pump inhibitors • Pro-kinetic agents • metoclopramide (Reglan) 10 mg tid • Coating agents • sucralfate (Carafate) 1 gm b.i.d. Specific Treatment: H. Zoster/PHN Epidural Steroid Injection Specific Treatment Abdominal Pain Syndromes • Infectious diarrhea – Ciprofaxin 500 mg bid x 5d, TMP/SMX DS bid x 5d, or Metronidazole 500 mg tid x 10 d – Fluids – Loperamide (Imodium) 2 mg p each stool – Antispasmotics • Cholangitis/cholecystis – Cefuroxime +/or piperacillin +/or mexolcillin – Endoscopic sphincterotomy? (sclerosing cholangitis) • CMV iliitis/colitis – Ganciclovir (Cytovene), 1000 mg tid – Antispasmotics • Drug induced pancreatitis and visceromegaly – pentamidine, didanosine, deoxycytidine associated> resolve with discontinuance – Celiac plexus block Specific Treatment Anorectal Syndromes • • • • • Clindamycin + aminoglycoside Sitz baths I&D, surgery Topical lidocaine (2-5% gel) Glycerin/petrolatum/shark liver oil (Preparation H) • Hydrocortisone 1% • Witch Hazel (50%) (Tucks pads) Specific Treatment Peripheral Neuropathies • Acute or Chronic Inflammatory Demyelinating Polyneuropathy – Plasmapheresis – Steroids – Zidovudine • Distal Symmetrical Polyneuropathy – – – – – – – TCA's (amitriptyline, nortriptyline, desipramine), SNRI's Anticonvulsants (gabapentin, carbamazepine) Tramadol Opioids Vitamin B & E supplementation Topical capsaicin or lidocaine (Lidoderm) Sympathetic neurolysis What medications are not effective in treating neuropathic pain? 1. TCA’s (e.g., amitriptyline, nortriptyline, etc) 2. SSRI antidepressants (e.g. Prozac, Paxil, etc.) 3. SNRI’s (e.g., Cymbalta, Effexor) 4. Opioids 5. Anti-epileptic medications (e.g. gabapentin) 6. Topical lidocaine and capsaicin Treatment Peripheral Neuropathies Efficacy Antineuropathic Medications Oral agents: TCA’s (2.64) > opioids (2.67) > gabapentin (4.29) > tramadol (4.76) > pregabalin (4.93) Topical agents: aspirin/diethyl ether (1.83) > lidocaine patch (2) > capsaicin (3.26) (Numbers needed to treat) e.g., PHN Specific Treatment Musculoskeletal system • Non-specific arthralgias – NSAID’s – Non-opioid analgesic • Reactive arthritis – Methotrexate (Rheumatrex) 2.5-10 mg/wk – Intra-articular steroid injections • Myopathies – – – – NSAID’s Non-opioid analgesic AZT Steroids • Zidovudine myositis: discontinue if possible Specific Treatment Arthridites Hip and SIJ Intra-articular Injections Summary Pain & Palliative Care in HIV/AIDS • – Prevalence – Barriers – Common HIV painful syndrome – Nociceptive vs. neuropathic – Dx specific process – NSAID’s, opioids, anti-neuropathic medications Recognition • • Thorough assessment Systemic pharmacotherapy • • Syndrome specific therapy Reassessment, adjustment, and empathy The End